To determine whether or not the timing of heparin infusion affects either bleeding or reocclusion following intracoronary streptokinase for acute myocardial infarction, heparin was infused immediately after streptokinase in 89 patients and was delayed for 12 hours in the subsequent 93. Bleeding occurred in 22 immediate-heparin patients and was major in five (one fatal); there were 14 hemorrhages in the delayed-heparin group, all minor. At discharge, reocclusions were observed in 18% (12/68) of immediate-heparin patients, and 11% (3/27) of the latter. Bioassayed fibrinogen levels displayed sustained depression regardless of bleeding for 20 hours after streptokinase; however, defibrinogenation measured by immunoassay was much less striking. This suggests that high levels of fibrinogen degradation products spuriously affect the bioassay of fibrinogen. We conclude that bleeding is related to the anticoagulant effects of fibrinogen degradation products interacting with heparin, and may be largely independent of hypofibrinogenemia. Delaying heparin for 12 hours may decrease the risk of bleeding while little affecting the risk of reocclusion.